The relative myocardial blood volume differentiates between hypertensive heart disease and athlete's heart in humans

Aims The adaptation of the myocardial microcirculation in humans to pathologic and physiologic stress has not been examined in vivo so far. We sought to test whether the relative blood volume (rBV) measured by myocardial contrast echocardiography (MCE) can differentiate between left ventricular (LV) hypertrophy (LVH) in hypertensive heart disease and athlete's heart. Methods and results Four groups were investigated: hypertensive patients with LVH (n=15), semi-professional triathletes with LVH (n=15), professional football players (n=15), and sedentary control individuals without cardiovascular disease (n=15). MCE was performed at rest and during adenosine-induced hyperaemia. The rBV (mL mL−1), its exchange frequency (β, min−1), and myocardial blood flow (mL min−1 g−1) were derived from steady state and refill sequences of ultrasound contrast agent. Hypertensive patients had lower rBV (0.093±0.013 mL mL−1) than triathletes (0.141±0.012 mL mL−1, P<0.001), football players (0.129±0.014 mL mL−1, P<0.001), and sedentary individuals (0.126±0.018 mL mL−1, P<0.001). Conversely, the exchange frequency (β) was significantly higher in hypertensive patients (11.3±3.8 min−1) than in triathletes (7.4±1.8 min−1), football players (7.7±2.3 min−1), and sedentary individuals (9.0±2.5 min−1). An rBV below 0.114 mL mL−1 distinguished hypertensive patients and triathletes with a sensitivity of 93% and a specificity of 100%. Conclusion Pathologic and physiologic LVH were differentiated non-invasively and accurately by rBV, a measure of vascularisation assessed by MC

C. elegans genome-wide analysis reveals DNA repair pathways that act cooperatively to preserve genome integrity upon ionizing radiation.

Ionizing radiation (IR) is widely used in cancer therapy and accidental or environmental exposure is a major concern. However, little is known about the genome-wide effects IR exerts on germ cells and the relative contribution of DNA repair pathways for mending IR-induced lesions. Here, using C. elegans as a model system and using primary sequencing data from our recent high-level overview of the mutagenic consequences of 11 genotoxic agents, we investigate in detail the genome-wide mutagenic consequences of exposing wild-type and 43 DNA repair and damage response defective C. elegans strains to a Caesium (Cs-137) source, emitting γ-rays. Cs-137 radiation induced single nucleotide variants (SNVs) at a rate of ~1 base substitution per 3 Gy, affecting all nucleotides equally. In nucleotide excision repair mutants, this frequency increased 2-fold concurrently with increased dinucleotide substitutions. As observed for DNA damage induced by bulky DNA adducts, small deletions were increased in translesion polymerase mutants, while base changes decreased. Structural variants (SVs) were augmented with dose, but did not arise with significantly higher frequency in any DNA repair mutants tested. Moreover, 6% of all mutations occurred in clusters, but clustering was not significantly altered in any DNA repair mutant background. Our data is relevant for better understanding how DNA repair pathways modulate IR-induced lesions

Constant-Time Arithmetic for Safer Cryptography

The humble integers, $\mathbb{Z}$, are the backbone of many cryptosystems. When bridging the gap from theoretical systems to real-world implementations, programmers often look towards general purpose libraries to implement the arbitrary-precision arithmetic required. Alas, these libraries are often conceived without cryptography in mind, leaving applications potentially vulnerable to timing attacks. To address this, we present saferith, a library providing safer arbitrary-precision arithmetic for cryptography, through constant-time operations. The main challenge was in designing an API to provide this functionality alongside these stronger constant-time guarantees. We benchmarked the performance of our library against Go\u27s big.Int library, and found an acceptable slowdown of only 2.56x for modular exponentiation, the most expensive operation. Our library was also used to implement a variety cryptosystems and applications, in collaboration with industrial partners ProtonMail and Taurus. Porting implementations to use our library is relatively easy: it took the first author under 8 hours to port Go\u27s implementation of P-384

Chapter 6 Kindergarten educators’ affective-motivational dispositions

Affective-motivational dispositions regarding the fostering of mathematics are an important aspect of early educators' professional competence, as educators are not following curricular programmes but need to seize moments in everyday activities and in play in order to foster mathematics. A variety of scales measuring variables of affective-motivational dispositions within a questionnaire were employed in a binational study involving 132 kindergarten educators in Germany and Switzerland. Based on the expectancy-value theory of motivation, the relations between educators' emotions regarding mathematics at school, the enthusiasm for mathematics as a subject, the value placed on mathematics and the expectancy of fostering mathematics successfully (self-efficacy) as well as the enthusiasm for fostering mathematics in kindergarten are examined. Following the analysis of correlations and the testing of a multiple regression model, it was found that enthusiasm for mathematics as a subject, importance of mathematics as a subject in kindergarten and self-efficacy predict enthusiasm for fostering mathematics, whereas the variable emotions regarding mathematics at school does not increase the variance explained. Self-efficacy, importance given to mathematics and enthusiasm for fostering mathematics are slightly higher in Switzerland than in Germany, which could be interpreted in light with the structural differences regarding kindergarten

Teaching quality in kindergarten: professional development and quality of adaptive learning support enhances mathematical competency

Adaptive learning support provided by kindergarten teachers before and after (macro-adaptive learning support) as well as during mathematical learning activities (micro-adaptive learning support) is a cross-cutting concept of teaching quality. Effective adaptive learning support enhances children’s learning. However, providing it is challenging and teachers need professional development (PD) to improve the quality of their support. This study investigates the mediating role of teaching quality between PD programs for kindergarten teachers and the development of children’s mathematical competency. 122 kindergarten teachers and their 825 pupils participated in the study. The teachers were randomly assigned to three groups. Two groups attended PD sessions designed to foster either macro- or micro-adaptive learning support. The third was the materials-only control group. The data was analyzed using a self-developed rating instrument focusing on generic and domain-specific elements of teaching quality related to macro- and micro-adaptive learning support. The multilevel latent change model analysis revealed that the PD programs had positive and significant effects on the teaching quality of kindergarten teachers. A significant positive relationship was also found between micro-adaptive learning support and changes in children’s mathematical competency. However, an indirect effect of teaching quality could not be detected, and the PD programs did not have a total effect on children’s mathematical competency. The study reinforces the importance of PD that specifically targets macro- and micro-adaptive learning support for kindergarten teachers. The mediation between PD and mathematical competency development requires further investigation

Development of an inhibiting antibody against equine interleukin 5 to treat insect bite hypersensitivity of horses

Insect bite hypersensitivity (IBH) is the most common allergic skin disease of horses. It is caused by insect bites of the Culicoides spp. which mediate a type I/IVb allergy with strong involvement of eosinophil cells. No specific treatment option is available so far. One concept could be the use of a therapeutic antibody targeting equine interleukin 5, the main activator and regulator of eosinophils. Therefore, antibodies were selected by phage display using the naïve human antibody gene libraries HAL9/10, tested in a cellular in vitro inhibition assay and subjected to an in vitro affinity maturation. In total, 28 antibodies were selected by phage display out of which eleven have been found to be inhibiting in the final format as chimeric immunoglobulin G with equine constant domains. The two most promising candidates were further improved by in vitro affinity maturation up to factor 2.5 regarding their binding activity and up to factor 2.0 regarding their inhibition effect. The final antibody named NOL226-2-D10 showed a strong inhibition of the interleukin 5 binding to its receptor (IC50 = 4 nM). Furthermore, a nanomolar binding activity (EC50 = 8.8 nM), stable behavior and satisfactory producibility were demonstrated. This antibody is an excellent candidate for in vivo studies for the treatment of equine IBH

Nestemäisten jätteiden vastaanotto ja käsittely Tarastenjärven jätekeskuksessa : Selvitys vaihtoehtoisista menetelmistä

Nestemäiset jätteet ovat erilaisia loka-autoilla kuljetettavia jätteitä, jotka koostuvat nesteestä ja kiintoaineksesta. Tällaisia jätteitä ovat esimerkiksi hiekan- ja rasvanerotuskaivoista imetyt nesteet sekä teollisuudessa syntyvät jätevesilietteet. Nestemäisiä jätteitä ei ole Valtioneuvoston päätöksestä enää vuoden 2002 jälkeen saanut sijoittaa sellaisenaan kaatopaikkapenkkaan, vaan ne on tullut esikäsitellä nesteen poistamiseksi. Tähän asti nestemäiset jätteet on käsitelty Tarastenjärven jätekeskuksessa painovoimaisesti erottelemalla. Menetelmä on ollut toimiva, mutta on päivityksen tarpeessa. Tämän opinnäytetyön tarkoituksena olikin tutkia erilaisia vaihtoehtoja nestemäisten jätteiden vastaanotolle sekä käsittelylle Tarastenjärven jätekeskuksessa, sekä arvioida eri vaihtoehtojen kustannuksia mikäli mahdollista. Myös tarvetta haitta-aineiden, kuten metallien ja öljyjen poistamiselle tutkittiin. Työn laatimisessa hyödynnettiin olemassa olevaa tieteellistä kirjallisuutta sekä asiantuntijahaastatteluja. Työn tilaajana toimi Pirkanmaan Jätehuolto Oy. Selvitystyön tuloksena kävi ilmi, että yleisimmät menetelmät nesteiden ja kiinteiden ainesten erottamiseen ovat painovoimainen erottelu ja suodatus. Painovoimaiset erottelijat ovat useimmiten kiinteäseinäisiä altaita, joissa kiintoaines laskeutuu painovoimaisesti altaan pohjalle ja pinnalle jäänyt kirkastunut neste ohjataan ylivuotona jatkokäsittelyyn. Kiintoaineksen ollessa kevyempää kuin vesi, se erottuu nesteen pinnalle. Suodattimien toiminta taas perustuu puoliläpäisevään suodatusmediaan, joka päästää nesteen läpi, mutta jättää kiintoaineksen suodattimeen. Suodattimet voivat olla esimerkiksi paineistettuja tai painovoimalla toimivia. Geotuubit ovat eräänlaisia paineistettuja säkkisuodattimia, joita on käytössä myös jätekeskuksissa. Useissa käsittelymenetelmissä käytetään apuna myös saostuskemikaaleja, jotka edistävät kiintoaineksen erottumista nesteestä. Haitta-aineiden osalta helpoin ratkaisu on poistaa ne kiintoaineksen mukana ja käsitellä ne pilaantuneiden maiden kanssa jätekeskuksessa. Mikäli haitta-aineet ovat nesteessä liukoisessa muodossa, voidaan apuna käyttää saostuskemikaaleja, kuten alumiini- tai rautasuoloja. Öljyjen erottamisessa olisi mahdollista hyödyntää öljynerotuskaivoa. Kirjallisuuden sekä haastattelujen perusteella päivitetty versio painovoimaisesta erottelujärjestelmästä sekä geotuubimenetelmä vaikuttavat parhailta käytettävissä olevilta ratkaisuilta. Suurin haaste jätekeskuksen nestemäisten jätteiden käsittelyssä on kuitenkin se, että nesteiden ominaisuudet eroavat kuormittain hyvin paljon toisistaan. Tähän voitaisiin vaikuttaa jätteiden tarkemmalla lajittelulla vastaanottovaiheessa. Käsittelymenetelmää valittaessa tulee kuitenkin pohtia järjestelmän kuluja sekä hyötyjä pitkällä aikavälillä niin, että päästään parhaaseen mahdolliseen puhdistuslopputulokseen.Liquid wastes are solid-liquid mixtures such as wastes from sand and grease separation wells and industrial wastewaters. Since 2002 liquid wastes have no longer been allowed to be placed at a waste disposal site according to the decree 1049/1999 of the Finnish Council of State. Therefore liquid wastes have to be dewatered before final disposal. At the moment liquid wastes are treated at the Tarastenjärvi waste management centre with gravitational separation but the system needs updating. The aim of this study was to provide Pirkanmaan Jätehuolto Oy with different methods of liquid waste handling as well as evaluate the costs of a new system if possible. Also the need for contaminant removal was taken into consideration. The study was carried out by literature reviews and interviewing professionals of the industry. The results showed that the most common methods of solid-liquid separation are gravitational separation and filtration. Gravitational separators are usually containers in which the solid matter is allowed to separate either by sedimentation or flotation. Filters have a semi-permeable filter media which traps the solid matter but allows the liquid to flow through. Geotubes are an example of filters that are currently being used in several waste management centres. Many separation methods also require the use of polymers or flocculants to operate effectively. When contaminants are in a settleable form they are rather easy to be removed and treated with the solid matter. If the contaminants are dissolved in the liquid it might be possible to make them settle by adding aluminium or iron sulphate. Also an oil separation well could be used to separate oils from the liquid phase. Based on the literature reviews and interviews an upgraded gravitational system or the geotube method seem to be the best options. However, more tests should be conducted to see if these methods would work in practice. The biggest challenge is that the incoming liquid waste loads at Tarastenjärvi are not homogenous which makes it difficult to choose a solution that works well for all of them. The situation could be improved with more precise classification of the waste loads and handling them separately according to their characteristics. The most important aspect is to find a long-term cost-effective solution that can provide sufficient handling of the liquid wastes

Stabilizing enzymes within polymersomes by co-encapsulation of trehalose

Enzymes are essential biocatalysts and very attractive as therapeutics. However, their functionality is strictly related to their stability, which is significantly affected by the environmental changes occurring during their usage or long-term storage. Therefore, maintaining the activity of enzymes is essential when they are exposed to high temperature during usage or when they are stored for extended periods of time. Here, we stabilize and protect enzymes by coencapsulating them with trehalose into polymersomes. The anhydrobiotic disaccharide preserved up to about 81% of the enzyme's original activity when laccase/trehalose-loaded nanoreactors were kept desiccated for 2 months at room temperature and 75% of its activity when heated at 50 °C for 3 weeks. Moreover, the applicability of laccase/trehalose-loaded nanoreactors as catalysts for bleaching of the textile dyes orange G, toluidine blue O, and indigo was proven. Our results demonstrate the advantages of coencapsulating trehalose within polymersomes to stabilize enzymes in dehydrated state for extended periods of time, preserving their activity even when heated to elevated temperature

Glacier contributions to river discharge during the current Chilean megadrought

The current Chilean megadrought has led to acute water shortages in central Chile since 2010. Glaciers have provided vital fresh water to the region’s rivers, but the quantity, timing and sustainability of that provision remain unclear. Here we combine in-situ, remote sensing and climate reanalysis data to show that from 2010 to 2018 during the megadrought, unsustainable imbalance ablation of glaciers (ablation not balanced by new snowfall) strongly buffered the late-summer discharge of the Maipo River, a primary source of water to Santiago. If there had been no glaciers, water availability would have been reduced from December through May, with a 31 ± 19% decrease during March. Our results indicate that while the annual contributions of imbalance ablation to river discharge during the megadrought have been small compared to those from precipitation and sustainable balance ablation, they have nevertheless been a substantial input to a hydrological system that was already experiencing high water stress. The water-equivalent volume of imbalance ablation generated in the Maipo Basin between 2010 and 2018 was 740 × 106 m3 (19 ± 12 mm yr-1), approximately 3.4 times the capacity of the basin’s El Yeso Reservoir. This is equivalent to 14% of Santiago’s potable water use in that time, while total glacier ablation was equivalent to 59%. We show that glacier retreat will exacerbate river discharge deficits and further jeopardise water availability in central Chile if precipitation deficits endure, and conjecture that these effects will be amplified by climatic warming